We plan to concentrate on the mechanisms whereby different macronutrients cause satiation. Until now we have used only glucose as the carbohydrate representative. In order to understand the way in which carbohydrates will operate we will compare glucose with isotonic fructose and galactose. These are hexoses that are metabolized but have different absorption rates and affect enzyme and hormone systems differentially. As the vagus is essential for glucose induced suppression of feeding, these comparisons will be made in vagotomized and intact animals. The effects of vagotomy and lateral hypothalamic lesions appear to not only eliminate glucose induced satiety but also result in an animal where glucose enhances food intake. Thus, we plan to look at the effects of glucose infusions on insulin and glucagon secretion after various central lesions and visceral denervation procedures. Radioimmunoassay techniques will be used. The locus of glucose satiating effectiveness we have discovered is a function of food deprivation and is correlated with liver glycogen levels. We are now looking more closely at possible liver enzyme inhibition and activation for possible clues to the nature of the satiety signal induced by glucose. Meal patterning will be analyzed in depth to understand the nature of the effects of presumed satiating substances.